Duchenne Muscular Dystrophy Fatigue Trajectories.

INTRODUCTION: Children with Duchenne muscular dystrophy (DMD) are at risk of experiencing fatigue that negatively impacts their health-related quality of life (HRQoL). This study aimed to assess the association between fatigue and HRQoL, by examining fatigue trajectories over 48 weeks, and assessing factors associated with these fatigue trajectories. METHODS: The study sample consisted of 173 DMD subjects enrolled in a 48-week-long phase 2 clinical trial (NCT00592553) for a novel therapeutic who were between the ages of 5 and 16 years. RESULTS: The results of regression modeling show baseline fatigue and baseline HRQoL (R 2 = 0. 54 for child self-report and 0.51 for parent proxy report) and change in fatigue and HRQoL over 48 weeks (R 2 = 0.47 for child self-report and 0.36 for parent proxy report) were significantly associated with one another. Three unique fatigue trajectories using Latent Class Growth Models were identified for child and parent proxy reported fatigue. The risk of being in the high fatigue group as compared to the low fatigue group increased by 24% with each year increase in age and also with decreasing walking distance, as reported by children and parent proxy, respectively. CONCLUSION: This study identified fatigue trajectories and risk factors associated with greater fatigue, helping clinicians and researchers identify the profile of fatigue in DMD children.

Duchenne muscular dystrophy respiratory profiles from real world registry data.

INTRODUCTION: Understanding real-world profiles from neuromuscular databases is helpful for optimizing clinical care and planning research studies. The Canadian Neuromuscular Disease Registry (CNDR) has respiratory data from a population of boys with Duchenne Muscular Dystrophy (DMD). OBJECTIVES: To describe cross-sectional respiratory profiles from a national DMD real-world dataset. To explore the relationship between forced vital capacity percent predicted (FVC%) and disease severity parameters: scoliosis, ambulation and ventilation status. METHODS: Descriptive statistics summarized the respiratory profiles. The CNDR registry enrolls and collects DMD clinic data from 36 Canadian centers. RESULTS: There were 414 participants enrolled. The age ranged from 2 to 36 years old. Pulmonary function test data were available for 323 participants. The use of ventilatory support was seen in a significant proportion (19.5%) of subjects by age 14-16 years and was used by the majority (69.2%) by age 20-22 years. FVC% declined at a rate of 3.19% per year with every 1-year increase in age. FVC% declined annually by 2.47% in nonambulatory participants versus by 0.96% in ambulatory participants. FVC% did not significantly change over age with the presence of scoliosis or use of ventilatory technology. CONCLUSIONS: The data from this large cohort are valuable for understanding real-world patterns of clinical care and disease progression. There is a significant association between the loss of ambulation and the rate of FVC% decline. Further longitudinal studies are needed to better understand the impact of disease parameters on pulmonary function decline and the need for ventilatory support.

The discovery of the DNA methylation episignature for Duchenne muscular dystrophy.

Duchenne Muscular Dystrophy (DMD) is an X-linked recessive neuromuscular disorder characterized by progressive muscle weakness due to loss of function mutations in the dystrophin gene. Variation in clinical presentation, the rate of disease progression, and treatment responsiveness have been observed amongst DMD patients, suggesting that factors beyond the loss of dystrophin may contribute to DMD pathophysiology. Epigenetic mechanisms are becoming recognized as important factors implicated in the etiology and progression of various diseases. A growing number of genetic syndromes have been associated with unique genomic DNA methylation patterns (called "episignatures") that can be used for diagnostic testing and as disease biomarkers. To further investigate DMD pathophysiology, we assessed the genome-wide DNA methylation profiles of peripheral blood from 36 patients with DMD using the combination of Illumina Infinium Methylation EPIC bead chip array and EpiSign technology. We identified a unique episignature for DMD that whose specificity was confirmed in relation other neurodevelopmental disorders with known episignatures. By modeling the DMD episignature, we developed a new DMD episignature biomarker and provided novel insights into the molecular pathogenesis of this disorder, which have the potential to advance more effective, personalized approaches to DMD care.

Amblyopia risk factors among pediatric patients in a hospital-based setting using photoscreening.

PURPOSE: The aim of our study was to determine the prevalence of amblyopia risk factors in children visiting the American University of Beirut Medical Center (AUBMC) using automated vision screening. METHODS: This was a hospital-based screening of 1102 children aged between 2 and 6 years. Vision screening was performed using PlusoptiX S12 over 2 years (2018-2020). The need for referral to a pediatric ophthalmologist was based on the amblyopia risk factors set forth by the American Association for Pediatric Ophthalmology and Strabismus. Referred patients underwent a comprehensive eye examination. RESULTS: A total of 1102 children were screened, 63 were referred for amblyopia risk factors (5.7%); 37/63 (59%) underwent comprehensive eye examination and 73% were prescribed glasses. Of the non-referred group of children, 6.35% had astigmatism, 6.25% were hyperopic and 3.27% were myopic. The refractive errors observed among the examined patients were distributed as follows: 41% astigmatism, 51% hyperopia, and 8% myopia; amblyopia was not detected. Refractive amblyopia risk factors were associated with the presence of systemic disorders. Bland-Altman plots showed most of the differences to be within limits of agreement. CONCLUSION: Using an automated vision screener in a hospital-based cohort of children aged 2 to 6 years, the rate of refractive amblyopia risk factors was 5.7%. Hyperopia was the most commonly encountered refractive error and children with systemic disorders were at higher risk.

High-Dose Levetiracetam for Neonatal Seizures: A Retrospective Review.

BACKGROUND: Neonatal seizures are frequently encountered in the neonatal intensive care unit and may be associated with serious long-term neurological sequelae. Response to treatment continues to be modest, and treatment guidelines remain unclear. The use of levetiracetam has been on the rise in the past several years due to its favorable safety profile in the face of limited data on its efficacy and optimal dosing regimens. Unlike the older age groups, the benefit of escalating to high-dose levetiracetam of 80-100 mg/kg/day in neonates not responding to the standard used dosing regimen (40-60 mg/kg/day) is not studied. We sought to investigate the safety and efficacy of levetiracetam escalation to high dose regimens for neonatal seizures. METHODS: A retrospective chart review over a 7-year period was conducted at the American University of Beirut to identify neonates with electrographically proven seizures treated with levetiracetam. Data was collected on electroclinical seizure characteristics, underlying etiology, seizure control, other anti-seizure medications, and adverse effects. RESULTS: Electronic chart review revealed a total of 15 neonates with electrographically confirmed seizures treated with levetiracetam, with escalation to high doses in seven. As a first line drug, levetiracetam monotherapy terminated seizures in six out 10 neonates, two of whom had complete seizure cessation only after escalation to high doses of 80 or 100 mg/kg/day. When used in combination with other anti-seizure medications, four out of five neonates achieved complete seizure cessation upon escalation to high doses of levetiracetam. No adverse effects were noted. CONCLUSIONS: In neonates not responding to the standard used levetiracetam doses, incremental increases to 80-100 mg/kg/day may be considered. Prospective studies are needed to confirm the promising role of such high dosing regimens, and to better elucidate the role of levetiracetam in neonatal seizures.